Cardiac and vascular disease (and, specifically, atherosclerosis) have emerged as the number one killer of modern man. It is a disease of multiple risk factors, but without a proven etiology.
Regarding the currently prevailing theory of cholesterol metabolism Disarray as the most important causative factor in the genesis of cardiac and vascular disease, it is remarkable that no one has ever proposed a logical justification for the existence of increased cardiovascular risk linked to the presence of increased cholesterol. The presence of such an ontological explanation would serve to bolster the selection of cholesterol as a causative factor, rather than merely as a factor associated with increased risk of vascular disease.
It is obvious, on the other hand, why animals of many species should have inordinately high platelet counts, in excess of what might be physiologic for long mammalian lives. Even while human beings had developed the genetic capacity for long lives in prehistoric times, trauma and infection were by far the most important mechanisms of demise. Life expectancies did not pass the three decade mark in many societies until the mid 19th century and continue to remain around this figure in several undeveloped nations today. Given these factors, it is obvious that the ability to achieve rapid and effective hemostasis would far outweigh the need for reduced intravascular events in nature. It is thus logical to assume that if the coagulation cascade can be demonstrated to be a participant in the development of vascular disease—which it is known to be—then it is likely that the survival traits of rapid hemostasis have long been in conflict with the requirements of long term patency. In other words, the “coagulation thermostat” has been selected for maximum rapidity and efficacy and this is in direct conflict with what is required for optimal blood vessel patency.
It is recognized from the experience of the primary applicant of this patent, as well as multiple other cardiovascular physicians that no patient with normally functioning platelets and chronic counts significantly below normal has ever presented with cardiovascular disease, acute or chronic. In addition, it is known that patients with Glanzmann's thrombasthenia, a genetic abnormality preventing platelet activation, are also immune to this disease. It is further known that patients undergoing cardiovascular by pass (“perfusion”) and extra-corporeal membrane oxygenation for the purpose of cardiothoracic surgery experience a phenomenon known as “pump head”, heretofore of unknown etiology, but logically due to activated and microaggregated platelet clusters. Finally, it is fact that the process of hemodialysis activates platelets in a manner similar to the cardiovascular by pass machines—to the extent that most patients need to be heparinized—and that patients on hemodialysis have tremendously accelerated progression of atherosclerosis.
As is outlined above, clinical observations, as well as basic research, confirm that platelets have the ability to initiate inflammation and/or induce vascular damage. Activated platelets are not only more likely to do this, but they also release neurohumors that linger and alter the function of blood. It is further known that platelets are the most unstable of all cells in the body (Ref. 1, 2). Even machines designed for the expressed purpose of platelet separation also cause significant degrees of platelet activation (at least 13% during the full separation by one account—Reference 3). This is because platelets are sticky, fragile and have multiple modes of activation. It is also due to the fact that prior art refers only to various centrifuge-based separation of platelets. Differential current and/or mixed phase processes are much more likely to effect rapid separation without current levels of platelet activation.
Substances released by activated platelets and retained in blood products also contribute to transfusion reactions, the onset or exacerbation of congestive heart failure, pneumonitis, pneumonia or other respiratory distress, as well as worsening of Systemic Inflammatory Response (SIRS) and frank sepsis.
Further, there is evidence that the initial establishment of tumors is not possible without angiogenesis. In addition, there is evidence that thrombin receptors have a role in this initial angiogenesis. Platelets have a role in modulation of thrombin receptors. Reduction of platelets to safe levels would affect thrombin receptor levels.
Finally, for anyone in doubt of the veracity of the potency of platelet effect on fibroblast growth and selected cellular activity, refer to U.S. Pat. No. 5,165,938. Platelet extracts cause visible increase in fibroblast activity that can be demonstrated through gross cell culture assays. Platelets (and compounds released by platelets) have a similar inflammatory effect on white cells and multiple other blood and vascular components.
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